Control the epithelial barrier: A pivotal first line of defense (Part 4)
Likewise activation of proteinase-activated receptor 1 on SCBN cells results in altered ZO-1 distribution and decreased barrier function that were prevented by pretreatment with inhibitors of caspase-3 or MLCK activation. This begs the question: is the increase in epithelial permeability observed following Giardia infection due to a parasite-derived proteinase? An intriguing possibility! Moreover, these observations show that several mechanisms contribute to the maintenance or disruption of epithelial barrier function – in this instance, physiological contraction of the enterocyte cytoskeleton and induction of programmed cell death – and also suggest that common mechanisms of barrier control might be mobilized in a variety of physiological and pathophysiological instances. This could allow physicians to modulate disease by controlling epithelial barrier function.
This is an elegant study integrating in vivo with in vitro work and will leave the reader with no doubt that Giardia infection can directly affect epithelial permeability via activation of MLCK (and caspase-3 ). The outstanding issues are: can the data gleaned from the SCBN cell culture model be applied to G muris-induced barrier disruption in mice and, if so, will the observations hold true for the human giardiasis and perhaps other enteropathies? This work both complements and extends that of other investigators in the field, and highlights MLCK and caspase-3 as potential targets for pharmacological modulation of epithelial permeability. It’s your time to experience safe and affordable treatment the way it was meant to be enjoyable. You can have that every time you order levitra sale at the best pharmacy that you are now welcome to check out.